Expectancy and Treatment Interactions: A Dissociation between Acupuncture Analgesia and Expectancy Evoked Placebo Analgesia

Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, USA.
NeuroImage (Impact Factor: 6.36). 04/2009; 45(3):940-9. DOI: 10.1016/j.neuroimage.2008.12.025
Source: PubMed

ABSTRACT Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects - including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) - interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture+high expectation and sham acupuncture+high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).

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Available from: Randy Lyanne Gollub, Jul 30, 2015
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    • "However, the precise interplay of pharmacotherapy and cognitive factors is still insufficiently understood. Although drug and expectancy interactions have been observed in different fields [27] [29] [34] [54], few studies have so far examined the precise interplay of analgesic drug effects with expectations. A recent study has shown that positive and negative expectancies are able to modulate the analgesic treatment outcome during an infusion of the l-opioid-receptor agonist remifentanil [9]. "
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    ABSTRACT: We investigated a possible interaction between topic analgesic treatment and treatment expectation on pain at the behavioral and neuronal level by combining topical lidocaine-prilocaine treatment with an expectancy manipulation in a 2-by-2 within-subject design (open treatment, hidden treatment, placebo, control). 32 healthy subjects received heat pain stimuli on capsaicin pretreated skin and rated their experienced pain during functional magnetic resonance imaging. This allowed us to separate drug- and expectancy-related effects at the behavioral and neuronal level and to test whether they interact during the processing of painful stimuli. Pain ratings were reduced during active treatment and were associated with reduced activity in the anterior insular cortex. Pain ratings were lower in open treatment compared to the hidden treatment and related to reduced activity in the anterior insular cortex, the anterior cingulate cortex, the secondary somatosensory cortex and the thalamus. Testing for an interaction revealed that the expectation effect was significantly larger in the active treatment conditions compared to the no-treatment conditions and was associated to signal changes in the anterior insular cortex, the anterior cingulate cortex and the ventral striatum. In conclusion, this study shows that even in the case of a topic analgesic, expectation interacts with treatment at the level of pain ratings and neuronal responses in placebo-related brain regions. Our results are highly relevant in the clinical context as they show (i) that expectation can boost treatment and (ii) that expectation and treatment are not necessarily additive as assumed in placebo controlled clinical trials.
    Pain 09/2013; 155(1). DOI:10.1016/j.pain.2013.09.024 · 5.84 Impact Factor
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    • "Also, a recent systematic review of expectancy and acupuncture analgesia has called for better ways of assessing expectancy [8]. Most studies use crude measures of expectancy (interviews, questionnaires, or 5-point Likert scales) and turn them into high vs low expectancy [2] [5] [6] [16] [17] [19] [22] [31] [33]. However, it may be more precise to record expected pain ratings on a visual analog scale (VAS) and compare these to actual pain ratings [21] [27] [39] [40]. "
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    ABSTRACT: It is well known that acupuncture has pain-relieving effects, but the contribution of specific and especially non-specific factors to acupuncture analgesia is less clear. One hundred and one patients who developed pain ⩾ 3 on a visual analog scale (VAS, 0-10) following third molar surgery were randomized to receive active acupuncture, placebo acupuncture, or no treatment for 30 min with acupuncture needles with potential for double-blinding. Patients' perception of the treatment (active or placebo) and expected pain levels (VAS) were assessed prior to and halfway through the treatment. Looking at actual treatment allocation, there was no specific effect of active acupuncture (P = 0.240), but a large and significant non-specific effect of placebo acupuncture (P < 0.001), which increased over time. Interestingly, however, looking at perceived treatment allocation, there was a significant effect of acupuncture (P < 0.001) indicating that patients who believed they received active acupuncture had significantly lower pain levels than those who believed they received placebo acupuncture. Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings following both active and placebo acupuncture (up to 69.8%). This is the first study to show that under optimized blinding conditions non-specific factors such as patients' perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self-reinforcing effects in acupuncture treatment. To obtain an effect of acupuncture in clinical practice it may, therefore, be important to incorporate and optimize these factors.
    Pain 05/2013; 154(9). DOI:10.1016/j.pain.2013.05.008 · 5.84 Impact Factor
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    • "The rationale for this investigation was examination of brain placebo mechanisms in the clinical population and for the clinical trial setting in which they were studied. Existing studies have demonstrated the predictive role of brain networks to placebo response only in healthy subjects and specifically in response to placebo conditioning [26] [32] [46] [48]. However, there is no knowledge of brain-based placebo prediction in clinical populations, especially when tested in a clinical trial. "
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    ABSTRACT: A fundamental question for placebo research is whether such responses are a predisposition, quantifiable by brain characteristics. We examine this issue in chronic back pain (CBP) patients who participated in a double-blind brain imaging (functional magnetic resonance imaging) clinical trial. We recently reported that when the 30 CBP participants were treated, for 2weeks, with topical analgesic or no drug patches, pain and brain activity decreased independently of treatment type and thus were attributed to placebo responses. Here we examine in the same group brain markers for predicting placebo responses-that is, for differentiating between posttreatment persistent CBP (CBPp) and decreasing CBP (CBPd) groups. At baseline, pain and brain activity for rating spontaneous fluctuations of back pain were not different between the 2 groups. However, on the basis of brain activity differences after treatment, we identified that at baseline the extent of information shared (functional connectivity) between left medial prefrontal cortex and bilateral insula accurately (0.8) predicted posttreatment groups. This was validated in an independent cohort. Additionally, by means of frequency domain contrasts, we observe that at baseline, left dorsolateral prefrontal cortex high-frequency oscillations also predicted treatment outcomes and identified an additional set of functional connections distinguishing treatment outcomes. Combining medial and lateral prefrontal functional connections, we observe a statistically higher accuracy (0.9) for predicting posttreatment groups. These findings indicate that placebo response can be identified a priori at least in CBP, and that neuronal population interactions between prefrontal cognitive and pain processing regions predetermine the probability of placebo response in the clinical setting.
    Pain 09/2012; 153(12). DOI:10.1016/j.pain.2012.08.008 · 5.84 Impact Factor
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